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Volume: 12 Issue: 4 August 2014

FULL TEXT

CASE REPORT
Revision Liver Transplant For Persistent Infection and Localized Aspergillosis After Hepatic Artery Thrombosis

Early hepatic artery thrombosis after liver transplant may be complicated by aggressive aspergillosis and bacterial infections that may cause morbidity and mortality. The definitive treatment of hepatic artery thrombosis is revision transplant. However, sepsis may be a contraindication to revision transplant. A 37-year-old man developed hepatic artery thrombosis at 3 days after liver transplant. During the treatment of hepatic artery thrombosis, he developed multiple biliary, bacterial, and fungal infections. Evaluation showed aspergillosis with multiple intrahepatic abscesses. He was treated with antibiotic and antifungal drugs. Despite active sepsis, revision transplant was performed and the infection resolved. Although sepsis may be a contraindication for transplant surgery, revision transplant was successful, probably because the primary transplanted liver was the source of infection.


Key words : Acinetobacter baumannii, Aspergillus, Complications, Sepsis

Introduction

Liver transplant complicated by hepatic artery thrombosis is difficult to treat. Hepatic artery thrombosis may cause varied clinical problems from minimal signs to acute hepatic failure.1 After early hepatic artery thrombosis, bacterial or fungal infections may be very aggressive and may cause morbidity and mortality. After liver transplant, aspergillosis has poor outcome because of pneumonia or disseminated disease, but localized infection in the transplanted liver is uncommon.2 Although surgical and radiographic interventions may be helpful, definitive treatment is revision transplant. However, the timing of revision transplant may be a problem because of donor organ shortage and uncontrolled infection as a contraindication for transplant.

We treated a patient with multiple biliary, bacterial, and fungal infections after early hepatic artery thrombosis. The patient was treated successfully with antimicrobial therapy and revision liver transplant.

Case report

A 37-year-old man with end-stage liver disease secondary to autoimmune hepatitis underwent liver transplant in our center in October 2010. On postoperative day 3, he developed hepatic artery thrombosis. He was treated with thrombectomy and revision of the anastomosis. Liver biopsy showed ischemic injury and mild acute rejection. On day 7 after transplant, a computed tomography angiogram showed obstruction of the right branch of the hepatic artery, and 85% stenosis of the hepatic artery anastomosis. Percutaneous transluminal angioplasty and stent placement failed because of dissection and complete obstruction of the common hepatic artery. Despite treatment with recombinant tissue plasminogen activator, no flow was reestablished in the artery.

The patient was listed for revision transplant. However, abdominal ultrasonography 2 days later showed a fluid collection at the hilum of the liver, and bilious fluid (300 mL) was aspirated percutaneously and drained. The patient developed fever, but blood cultures showed no growth. The doses of cyclosporine, prednisolone, and mycophenolate mofetil were decreased, and he was treated with piperacillin, tazobactam, and amphotericin B. Within 2 weeks, the fever resolved. Abdominal computed tomography scan showed a mass (30 × 20 mm) at the hilum of the liver, and there was mild dilation of intrahepatic bile ducts. Endoscopic retrograde cholangiopancreatography showed a large defect at the common bile duct, but no stent could be inserted. A Roux-en-Y high hepaticojejunostomy was performed, and a biliary stent was passed through the anastomosis to drain the subhepatic area.

However, 2 weeks later, the patient again became febrile. Blood and drainage fluid cultures showed Escherichia coli and Klebsiella species. In addition, cytomegalovirus antigenemia was detected. Piperacillin and tazobactam were replaced with imipenem, ganciclovir was administered, and amphotericin B was continued. After 10 days, the fever resolved. At 55 days after primary liver transplant, a suitable donor was found and revision liver transplant was planned. However, the patient developed a massive right pleural effusion, severe respiratory distress, sepsis, and intermittent fever despite the antimicrobial drugs. Surgery was canceled and a chest tube was inserted.

At 3 months after primary liver transplant, another suitable donor was found and revision liver transplant was performed. Intraoperative findings included localized infection at the hilum of the liver, necrotizing solid tissue, disruption of the choledochojejunostomy, and absence of a bile duct. After surgery, therapy included imipenem (1000 mg, 3 times daily), amphotericin B (1 mg/kg/d), tacrolimus, low-dose corticosteroids, and mycophenolate mofetil. Acinetobacter baumannii was isolated from drainage and pleural fluid. Histopathologic study of the excised liver showed diffuse necroinflammatory changes, massive necrosis, bile lakes consistent with deep mycosis, hepatic abscesses, septate hyphae, and gram-negative coccobacilli (Figures 1 and 2). Acinetobacter baumannii and Aspergillus organisms were cultured from abscesses of the excised liver. Voriconazole was not available, and antifungal treatment was changed from amphotericin B to itraconazole (200 mg, twice daily) after 2 weeks. The patient had an uneventful postoperative course until day 8, when he developed fever and a surgical wound infection from Acinetobacter baumannii. The wound was opened and the fever resolved within 2 days.

At 4 weeks after revision transplant, the patient was discharged home from the hospital. At 4 months after revision transplant, he developed acute moderate rejection that was confirmed with a liver biopsy. Treatment included a corticosteroid pulse (1000 mg) with antithymocyte globulin (75 mg daily for 10 days). He was discharged after 2 weeks, and he had normal liver enzymes on increased doses of maintenance drugs. At 2 years after revision transplant, the patient was alive with no further complications.

Discussion

Hepatic artery thrombosis may occur in 4% to 25% liver transplants and has 20% mortality.3 Hepatic artery thrombosis may be early or late, with a cutoff at 15, 30, or 60 days after liver transplant.3-5 Early hepatic artery thrombosis usually is treated surgically with thrombectomy and revision of the anastomosis, but treatment failure may occur in 20% to 60% patients.6 Percutaneous transluminal angioplasty may have 90% success for treatment of late hepatic artery thrombosis, but complications may include thrombosis and dissection of the artery.7 When all other treatment fails and hepatic artery thrombosis recurs, revision liver transplant may be the only effective treatment.8 In the present case, revision of the anastomosis was successful but stenosis occurred. In addition, percutaneous transluminal angioplasty and stent placement were complicated by intimal dissection and thrombosis, necessitating revision transplant.

Early hepatic artery thrombosis may be complicated by infections such as intrahepatic biloma or abscess, intermittent bacteremia, and sepsis.3 In this patient, the clinical condition deteriorated despite broad spectrum antibiotics, antifungal therapy, and reduction of the dosages of immunosuppressive drugs; intermittent fever was present and the collection resembled a biloma. The plan to perform revision transplant was debated because sepsis is an absolute contraindication for liver transplant.9 Nevertheless, revision transplant was performed despite active sepsis, and he had marked improvement in his clinical condition and resolution of sepsis. The most likely source of infection was the primary transplanted liver. Therefore, resistant infection in transplanted patients may originate from the liver and may resolve only after revision transplant.

In the present patient, histopathologic and microbiologic studies of the excised liver confirmed the diagnosis of aspergillosis and infection with Acinetobacter baumannii. Aspergillosis may occur in transplant recipients who have laparotomy after transplant, cytomegalovirus infection, prolonged hospitalization, or vascular complications and may occur concurrently with bacteremia.2,10,11 Invasive aspergillosis in transplant recipients may present with pneumonia, disseminated disease, an intra-abdominal collection, meningitis, or a wound infection. Diagnosis of invasive aspergillosis may be difficult because the infected organ may be inaccessible, precluding histopathologic evaluation for tissue invasion.2,12-14 In some cases, revision transplant may not resolve aspergillosis.2 Invasive aspergillosis may have high mortality (87%) in transplant recipients because of immunosuppression, delayed and unproven diagnosis, the invasive behavior of aspergillosis, and ineffectiveness of revision transplant.10,12,13 In this patient, aspergillosis was localized to the transplanted liver with a rare form of multiple intrahepatic abscesses.15 Therefore, although amphotericin B and local drainage were ineffective, revision transplant and removal of the infected primary transplanted liver resulted in complete resolution of aspergillosis.

In summary, aspergillosis after liver transplant may present rarely with multiple intrahepatic abscesses and persistent infection after hepatic artery thrombosis. Revision transplant may be effective treatment. Although, sepsis usually is a contraindication for transplant surgery, revision transplant in the present patient was successful, probably because the source of infection was the primary transplanted liver.


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Volume : 12
Issue : 4
Pages : 381 - 383
DOI : 10.6002/ect.2013.0129


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From the 1Department of General Surgery; the 2Hepatobiliary and Liver Transplantation Research Center; and the 3Department of Gastroenterology, Tehran University of Medical Sciences, Tehran, Iran
Acknowledgements: The study was not supported by any grants, and the authors have no conflicts of interest to declare.
Corresponding author: Amir Kasraianfard, Hepatobiliary and Liver Transplantation Research Center, Imam Khomeini Hospital Complex, End of Keshavarz Boulevard, Tehran, 1419733141 IR Iran
Phone: +98 21 6119 2659
Fax: +98 21 6658 1657
E-mail: amirkasraian@gmail.com